The onset of puberty is a consequence of an increase in the secretion of gonadotropin-releasing hormone (GnRH) from the GnRH-containing neurons in the hypothalamus. However, the mechanisms that drive the onset and progression of the pubertal increase in GnRH release are unknown. Using electrophysiological recordings and compartmental modeling, Specific Aim 1 tests the novel hypothesis that structural remodeling of the GnRH dendrites alters the biophysical characteristics of GnRH neurons in a fashion that facilitates repetitive action potential firing, the mode of neuronal activity that results in neuropeptide release. Specific Aim 2 will test the hypothesis that a sex difference in GABAergic inputs to GnRH neurons emerges during the peripubertal period and accounts for differences in tempo of the sexual maturation. Identifying the substrate that accounts for this difference and the mechanisms that modulate the peripubertal transition is a critical issue since the advancement of the onset of puberty in girls has broad implications for the health and well-being of young women. Specific Aim 3 will determine how key neurotransmitters control the transition in firing patterns of GnRH neurons at puberty. The principle investigators bring strengths from the critical perspectives of reproductive physiology, electrophysiological recordings from GnRH neurons, computational neuroscience and mathematics. The principle investigators will leverage and integrate these strengths and bring them to bear on a seminal question in mammalian development, the control of the sexual maturation. Taken together, the studies in this proposal will answer pivotal questions about the mechanisms and process that account for the onset of fertility. PUBLIC HEALTH RELEVANCE: Neurons contained within the brain region called the hypothalamus control sexual reproduction through the intermittent release of gonadotropin releasing hormone (GnRH). The goal of the present proposal is to understand how the activity of GnRH-containing neurons is controlled at the time of puberty, a major milestone in mammalian development.